With the global epidemic of obesity and diabetes, the burden of other chronic diseases is increasing. Nonalcoholic fatty liver disease (NAFLD) is one such disease that now has potentially enormous public health consequences. NAFLD is a leading cause of chronic liver disease and cirrhosis, affecting up to 30% of people in other countries. However, in the United States (U.S.) there are no reliable estimates of NAFLD prevalence. Depending on the diagnostic method, estimates range from 5 to 33%. The major risk factors for NAFLD include type 2 diabetes, obesity and insulin resistance. Yet the role of demographic, genetic and lifestyle factors in the development of NAFLD has not been studied in a nationally representative sample of the U.S. population. Finally, while NAFLD is thought to increase the risk of liver-related mortality, recent data suggest that NAFLD may also increase cardiovascular disease risk and mortality. Our overarching goals are to (1) better define the epidemiology of NAFLD in the general U.S. population, including describing the cross-sectional demographic, lifestyle and genetic correlates of NAFLD, and (2) assess whether NAFLD increases the risk of all-cause and cardiovascular mortality over time. To achieve these goals, the investigators propose to use existing data and images from The Third National Health And Nutrition Examination Survey (NHANES III) to construct the first nationally representative cohort study of NAFLD and related mortality. Specifically, NHANES III included standardized gallbladder ultrasounds which can be reread to detect hepatic steatosis and the findings linked to all NHANES III data. The proposed study has the following 3 specific aims: (1) Read the available NHANES III ultrasounds (N=14,294) to measure hepatic steatosis and link the results to other existing NHANES data;(2) Describe the epidemiology of NAFLD and its association with demographic characteristics, lifestyle-related factors and available genetic variants;and (3) Examine the independent contribution of NAFLD to the risk of subsequent all-cause and cardiovascular mortality after taking into account well established risk factors. This study will provide a population-wide estimate of the prevalence of NAFLD in the U.S., including data in key age, sex, and race subgroups as well as identify potentially novel lifestyle-related and genetic risk factors. Importantly, it will also estimate the risk of death among people with NAFLD. Finally, all the ultrasound data will be made publicly available, setting the stage for future investigation. PUBLIC HEALTH RELEVANCE: This study will help identify important risk factors for nonalcoholic fatty liver disease (NAFLD) in the general U.S. population and determine whether it increases the overall risk of death and death from cardiovascular disease. Since NAFLD is now a leading cause of chronic liver disease, this information is important to help find ways to prevent it, as well as track its effect on the population over time.